Ann Taylor sandbox 11

The Mechanism of Trypsin
Trypsin is a serine protease that is used in the digestive system. It cleaves on the C terminal side of arginine or lysine residues. This specificity is due to the presence of an aspartate residue at the bottom of the binding pocket.

Trypsin cleaves peptides via a covalent catalysis mechanism--that is, it forms a covalent intermediate between the substrate and itself, which is then cleaved by reaction with water. This structure shows the covalent interaction between trypsin and a small peptide, succinyl-ala-ala-pro-lys (pdb code 2agg). The catalytic triad of Serine 195, Histidine 57 and Aspartic acid 102 are the key residues involved in the mechanism. After binding to the substrate, serine 195 nucleophilically attacks the carbonyl group of the cationic amino acid of the substrate. His57 and asp102 assist in the catalysis by increasing the nucleophilicity of the serine residue and by donating a proton to the leaving peptide group. This dual role of deprotonating serine and protonating the leaving peptide is facilitated by a shift in the position of the His 57 residue.